Bone Abstracts

Background: Hypophosphatasia (HPP) is a disorder of bone mineralisation caused by deficiency of alkaline phosphatase (secondary to ALPL gene mutations), causing accumulation of inorganic pyrophosphate (PPi) thus inhibiting bone mineralisation. The perinatal form presents with severe manifestations at birth. Most severe skeletal manifestations are detectable by 20 weeks gestational age (GA) anomaly scan, and antenatal care within the UK practices routine detailed anomaly ultrasound scan (USS) at 20 weeks GA, with no further detailed scans until delivery if this is satisfactory. We describe a patient where there was a family history of HPP and antenatal scan at 20 weeks failed to detect any skeletal abnormalities.

Case history: Parents were known to be carriers of ALPL mutation. They had had a previous termination of an affected foetus. Detailed USS at 16 and 20 weeks GA were normal and therefore family decided to continue with pregnancy (Fig. 1A). Because of poor foetal growth a further USS was performed at 31 weeks GA, which showed poor skeletal mineralisation, micromelia and limb fractures (Fig. 1B). Genetic testing at 32 weeks GA confirmed HPP. This infant was born with severe skeletal manifestations of HPP (Fig. 1C). Asfotase alfa was initiated neonatally, resulting in survival of the infant and improvement of bone mineralisation (Fig. 1D).

Figure 1 Right tibia and fibula. A: Normal at 20 weeks GA; B: Fractures and rickets-like changes at 31 weeks GA; C: At birth, shows shortened and hypomineralised bones; D: Improvement in bone mineralisation following 5 months treatment with asfotase alfa.

Discussion: Skeletal features of perinatal HPP may not be apparent at 20 weeks USS. We speculate that foetal accumulation of PPi during pregnancy results in progressive skeletal demineralisation, which may only become apparent on USS in later pregnancy.

Conclusion: In the presence of a family history of HPP, we recommend antenatal genetic testing should be offered to families, as early USS cannot be relied upon for confirming diagnosis of perinatal HPP.

Disclosure: The authors declared no competing interests.